The mammalian molybdenum enzymes of mARC

J Biol Inorg Chem. 2015 Mar;20(2):265-75. doi: 10.1007/s00775-014-1216-4. Epub 2014 Nov 26.

Abstract

The "mitochondrial amidoxime reducing component" (mARC) is the most recently discovered molybdenum-containing enzyme in mammals. All mammalian genomes studied to date contain two mARC genes: MARC1 and MARC2. The proteins encoded by these genes are mARC-1 and mARC-2 and represent the simplest form of eukaryotic molybdenum enzymes, only binding the molybdenum cofactor. In the presence of NADH, mARC proteins exert N-reductive activity together with the two electron transport proteins cytochrome b5 type B and NADH cytochrome b5 reductase. This enzyme system is capable of reducing a great variety of N-hydroxylated substrates. It plays a decisive role in the activation of prodrugs containing an amidoxime structure, and in detoxification pathways, e.g., of N-hydroxylated purine and pyrimidine bases. It belongs to a group of drug metabolism enzymes, in particular as a counterpart of P450 formed N-oxygenated metabolites. Its physiological relevance, on the other hand, is largely unknown. The aim of this article is to summarize our current knowledge of these proteins with a special focus on the mammalian enzymes and their N-reductive activity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Coenzymes / chemistry*
  • Cytochromes b5 / chemistry
  • Cytochromes b5 / metabolism
  • Electron Transport
  • Humans
  • Mammals
  • Membrane Proteins / chemistry*
  • Membrane Proteins / metabolism
  • Metabolic Detoxication, Phase I
  • Metalloproteins / chemistry*
  • Mitochondria / enzymology
  • Mitochondrial Proteins / chemistry*
  • Mitochondrial Proteins / metabolism
  • Molybdenum / chemistry*
  • Molybdenum / metabolism
  • Molybdenum Cofactors
  • NAD / chemistry
  • Oxidoreductases / chemistry*
  • Oxidoreductases / metabolism
  • Pteridines / chemistry*

Substances

  • Coenzymes
  • Membrane Proteins
  • Metalloproteins
  • Mitochondrial Proteins
  • Molybdenum Cofactors
  • Pteridines
  • NAD
  • Molybdenum
  • Cytochromes b5
  • molybdenum cofactor
  • MTARC2 protein, human
  • Oxidoreductases
  • amidoxime reducing component, human